The Responsible Conduct of Research

1. The Responsible Conduct of Research Paul Braunschweiger Ph.D. Professor of Radiation Oncology Chair, University of Miami IACUC

2. Talking points What is RCR and why is it important New Guidelines, NSF, NIH. Intersection of RCR and Lab animal welfare. Resources for teaching the RCR

3. NSF Mandate for RCR Education August 20, 2009 NSF implementation of Section 7009 of the America Creating Opportunities to Meaningfully Promote Excellence in Technology, Education, and Science (COMPETES) Act (42 U.S.C. 1862o–1).http://edocket.access.gpo.gov/2009/pdf/E9-19930.pdf Requires that …..‘‘each institution that applies for financial assistance from the Foundation for science and engineering research or education describe in its grant proposal a plan to provide appropriate training and oversight in the responsible and ethical conduct of research to undergraduate students, graduate students, and postdoctoral researchers participating in the proposed research project.’’

4. NSF Mandate for RCR Education January 4, 2010, NSF will require that, at the time of proposal submission to NSF, a proposing institution’s Authorized Organizational Representative certify that the institution has a plan to provide appropriate training and oversight in the responsible and ethical conduct of research to undergraduates, graduate students, and postdoctoral researchers who will be supported by NSF to conduct research.

5. RCR 12-29-07 NSF Mandate for RCR Education • Content • No specific recommendation. • “Therefore, it is the responsibility of each institution to determine both the content and the delivery method for the training that will meet the institution’s particular needs for RCR training in all areas at that institution for which NSF provides support.” • Delivery method • No specific recommendations • “It will be up to each institution to determine how best to ensure effective and appropriate education in responsible research practices.”

6. NIH Mandate • Policy • NIH requires that all trainees, fellows, participants, and scholars receiving support through any NIH training, career development award (individual or institutional), research education grant, and dissertation research grant must receive instruction in responsible conduct of research.  This policy will take effect with all new and renewal applications submitted on or after January 25, 2010, and for all continuation (Type 5) applications with deadlines on or after January 1, 2011. • National Institutes of Health (NIH), NOT-OD-10-019, issued November 24, 2009.

7. RCR 12-29-07 NIH Mandate • National Institutes of Health (NIH), NOT-OD-10-019, November 24, 2009. • Develops principles on providing instruction in responsible conduct of research. • Specific about who should participate, how often instruction should occur, and the form that instruction should take; • Addresses issues that have arisen as the practice of biomedical, behavioral and clinical science has evolved • Provides guidance to applicants, peer reviewers and NIH staff in determining how well specific plans for instruction in responsible conduct of research compare with the best practices. NOT-OD-10-019, issued November 24, 2009.

8. RCR 12-29-07 Applicability • This Notice applies to: • All NIH Institutional Research Training Grants, • Individual Fellowship Awards, • Career Development Awards (Institutional and Individual), • Research Education Grants, • Dissertation Research Grants, • Other grant programs with a training component that requires instruction in responsible conduct of research as noted in the Funding Opportunity Announcement. NOT-OD-10-019, issued November 24, 2009.

9. RCR 12-29-07 Principles for the RCR • Responsible conduct of research is an essential component of research training.  Instruction in RCR is an integral part of all research training programs. Its evaluation will impact funding decisions. • Active involvement in the issues of responsible conduct of research should occur throughout a scientist’s career.  • Instruction in responsible conduct of research should therefore be appropriate to the career stage of the individuals receiving training. • Individuals supported by individual funding opportunities such as fellowships and career development awards are encouraged to assume individual and personal responsibility for their instruction in responsible conduct of research. NOT-OD-10-019, issued November 24, 2009.

10. RCR 12-29-07 Principles for the RCR • Research faculty of the institution should participate in instruction in RCR in ways that allow them to serve as effective role models for their trainees, fellows, and scholars. • Instruction should include face-to-face discussions by course participants and faculty; i.e., on-line instruction may be a component of instruction in responsible conduct of research but is not sufficient to meet the NIH requirement for such instruction, except in special or unusual circumstances. • Instruction in responsible conduct of research must be carefully evaluated in all NIH grant applications for which it is a required component. 

11. RCR 12-29-07 5 Instructional Components • Format • Face-to-face discussions among the participating trainees/fellows/scholars/participant. • While on-line courses can be a valuable supplement to instruction in responsible conduct of research, online instruction is not considered adequate as the sole means of instruction. NOT-OD-10-019, issued November 24, 2009.

12. RCR 12-29-07 Instructional Components 2. Subject Matter • While there are no specific curricular requirements for instruction in responsible conduct of research, the following topics have been incorporated into most acceptable plans for such instruction: • Conflict of interest – personal, professional, and financial • Human and non-human subjects welfare, and safe laboratory practices • Mentor/mentee responsibilities and relationships • Collaborative research including collaborations with industry • Peer review. • Data acquisition and management. • Research misconduct and reporting misconduct . • Responsible authorship and publication. • The scientist as a responsible member of society, contemporary ethical issues in biomedical research, and the environmental and societal impacts of scientific research NOT-OD-10-019, issued November 24, 2009.

13. RCR 12-29-07 Instructional Components • Faculty Participation • Training faculty and sponsors/mentors are highly encouraged to contribute both to formal and informal instruction in responsible conduct of research. Full faculty participation. • Duration of instruction • “Substantive contact hours”. Acceptable programs generally involve at least eight contact hours. • Semester long program maybe better than a one day 8 hr workshop. • Frequency of instruction. • “…at the undergraduate, post-baccalaureate, pre-doctoral, postdoctoral, and faculty levels.” • …. Instruction must be undertaken at least once during each career stage, and at a frequency of no less than once every four years. • Grant applications must address all 5 components. NOT-OD-10-019, issued November 24, 2009.

14. RCR 12-29-07 Peer review • Applications lacking a plan for instruction in responsible conduct of research will be considered incomplete and may be delayed in the review process or not reviewed. • Applications with a “Plan” • Reviewers will specifically address the five Instructional Components (Format, Subject Matter, Faculty Participation, Duration and Frequency) . • Review panel’s evaluation of the plan will not be a factor in the determination of the impact/priority score. • Plans and past record will be rated as ACCEPTABLE or UNACCEPTABLE. • Regardless of Priority Score, applications with unacceptable plans will not be funded until the applicant provides an acceptable, revised plan. 

15. RCR 12-29-07 Compliance NIH policy requires participation in and successful completion of instruction in responsible conduct of research by individuals supported by any NIH training/research education/fellowship /career award.  It is expected that course attendance is monitored and that a certificate or documentation of participation is available upon course completion.  NIH does not require certification of compliance or submission of documentation, but expects institutions to maintain records sufficient to demonstrate that NIH-supported trainees, fellows, and scholars have received the required instruction.

16. RCR 12-29-07 Resources The NIH Research Training website (http://grants.nih.gov/training/extramural.htm) includes additional information on instruction in responsible conduct of research. Office of Research Integrity (http://ori.hhs.gov/), links to instructional materials, and examples of programs that have been regarded as good models for instruction in responsible conduct of research (http://bioethics.od.nih.gov/researchethics.html).   The National Academy Press has just published the 3rd. edition of the classic, On Being a Scientist, and is available online at http://books.nap.edu/catalog.php?record_id=12192. The CITI Program www.citiprogram.org , On-line program in the RCR. Text, case studies, video vignettes and quizzes in the nine topic areas of RCR. Training data management. Responsible Conduct of Research Education Committee (RCREC) http://rcrec.org

17. What is the RCR What is involved in RCR education

18. Integrity & Responsible Conduct of Research • Accepted practices for the RCR can vary from discipline to discipline and even from laboratory to laboratory. • Some shared values for the RCR that bind all researchers together: • Honesty - conveying information truthfully and honoring commitments. • Accuracy- reporting findings precisely and taking care to avoid errors. • Efficiency -using resources wisely and avoiding waste. • Objectivity- letting the facts speak for themselves and avoiding improper bias. • Compliance with regulatory requirements to document ethical behavior. • Integrity in the Research “Integrity” Fredric Terral 2007

19. Integrity in Research Enterprise "Integrity Protecting the Works of Man." John Quincy Adams Ward, 1903  • Starts with Institutional Commitment • Promoted and nurtured by the IACUC, IRB, IBC, CoIC, ESCRO • Promotes of scientifically valid data • Avoids or minimizes all COIs • Embraced by the investigators, staff and students as, • “The right thing to do”

20. Why Does Integrity Matter in Research? • Puts subjects at risk. • Injures careers • Wastes Resources • Wastes Time • Undermines the Public Trust.

21. The Public Trust • The “Public” supports most of the research in the US. • Sponsored research is a privilege and not an entitlement. • Society Trusts investigators to conduct research ethically and responsibly. • Violation of the public’s trust, brings Regulation.

22. The Public Trust • New Regulations are not the result of good or ethical behavior. • Federal Regulations specifically require • Accountability • Documentation of ethical behavior • Regulatory requirements to document are designed to: • Help investigators conduct research responsibly. • Preserve the Public Trust in research. • Without the Public’s Trust there is no research

23. RCR 12-29-07 Betrayal of the Public Trust Brings Regulation • 1984 Univ. Penn. Head Trauma Study. • PETA and ALF alleges inhumane research practices. • Videos • NIH investigated. Research activities not conducted according the existing policies. • Lack of adequate anesthesia and analgesia. • Lack of sterile technique. • Lack of supervision by PI. • Lack of training of laboratory personnel. • NIH Shut down the project. • Research Project permanently shut down.

24. RCR 12-29-07 Consequences of betrayal of the Public Trust • Puts subjects at risk • Federal inquiry / intervention • Institutional embarrassment • Fines • Wasted resources • Personal embarrassment • Loss of funding, Loss of livelihood • Fines • Justification and / or vindication for groups with anti-research agenda. A.L.F.

25. The Foundation of Ethical Research Practices is Research Ethics Education

26. RCR 12-29-07 Promoting integrity in the Research Enterprise • Teaching the Responsible Conduct of Research • Books, Journal articles • Classroom experience • Seminars and conferences • Professional Societies • Web based courses and tutorials. • Mentoring

27. RCR 12-29-07 The Responsible Conduct of Research • Research Misconduct. • Data Acquisition and Management. • Responsible Authorship. • Conflicts of Interest. • Responsible Peer Review. • Human Subjects Protection. • Lab Animal Welfare. • Mentoring. • Responsible Collaborative Research. • Financial responsibility. • Environmental ethics.

28. RCR 12-29-07 Data Acquisition and Managementstudy design • Humane endpoints • Minimizing Pain and distress • Statistically justified sample size determinations. • Data security – • Photography and video in animal experimentation. • Data acquisition and usage, • Data obtained from studies where unapproved procedures have been used. • Pilot studies • When does a pilot study cease being a pilot study.

29. RCR 12-29-07 Responsible Authorship • Who on the research team deserves to be listed in the byline of the paper and who should be an author. • According to the ICMJE • Design of the experiments. • Writing and/or editing the paper • Approval of the manuscript before submission to the journal. • Which can can be ethically published. • Publishing negative data

30. Mentoring The social fabric of science Excellent approach to teaching research ethics and lab animal welfare.

31. The Ideal Mentor • “The truly complete mentor." This is "a single individual who is able to serve as an advisor/guide, developer of talent/coach, opener of doors/advocate, role model, interpreter of organizational or professional rules, protector, rule setter/boss - and carries on all of these functions on a long term basis." Ideal mentoring may require input from more than one person! Silen, "In Search of the Complete Mentor," in Mentations, Volume 5-Fall 1998,at http://www.hms.harvard.edu/dcp/mentations/fall_98/searchofmentor.html

32. RCR 12-29-07 Mentoring Most mentors are not well trained. Confusion, Res. Advisors vs. Mentors. Trainees often learn unethical practices and short cuts from the mentor / research advisor. Taking short cuts can get the students and fellows in trouble with the IACUC.

33. Conflicts of Interest and Commitment

34. Conflicts of Interest and Commitment • A conflict of interest is a situation in which financial or other personal considerations have the potential to compromise or bias professional judgment and objectivity. • The appearance of a conflict of interest is one in which a reasonable person would think that the professional's judgment is likely to be compromised. • A CoIexists whether or not decisions are affected by a personal interest. • A potential CoI involves a situation that may develop into an actual conflict of interest. • A CoI is not considered misconduct in research, since the definition for misconduct is currently limited to F.F&P. • A CoI could lead to misconduct.

35. Conflicts of Interest and Commitment. • Tangible conflicts of Interest • Investigator has a financial stake in the outcome of an experiment or trial. • CoIs require management strategies • Disclosure by the investigator, • CoIs managed by the institution, • Reported to the Feds.

36. WHAT DO THESE 4 PHYSICIANS HAVE IN COMMON Dr. CharlesNemeroff • Harvard University • $4 million in unreported consulting revenues from Pharmaceutical Industry. • Promoted antipsychotic drugs in children • GOV. GRANTS • Emory University • Took >$500K in unreported consulting income from Glaxo. • Gov. Funded research on Glaxo drugs

37. Conflicts of Interest and Commitment. • Conflicts of commitment. • Using institutional time for consulting. • Using institutional resources for personal gain. • Using graduate students/fellows for work on company projects. • Other intangible conflicts of interest. • Personnel and professional. • IACUC, IRB, ESCRO. • Personal relationships. Good and Bad. • Conflicts of conscience • Religious beliefs. • Philosophical differences (e.g., status of animals.)

38. CoI in Animal Research Program

39. Understanding and Managing the Conflict of Interest • The Public’s Interests • Society demands medical advances. • Society understands that animals as subjects: • Can not understand the research. • Can not consent to participate in what may cause them harm, pain or death. • Society demands documentation that animal research is ethically designed and conducted.

40. Understanding and Managing the Conflict of Interest • The investigator Interests • Get the data, publish the papers, get the grants, support their labs, get promoted, get a raise, buy the new boat. • The Interests of the Veterinarians • Animal welfare Vs. Helping investigators get their work done. • Veterinarians as co-investigators, coauthor. • Institutional interests • Institutions want the grants, patents and indirect costs. • IOs need to be willing to deal with problematic faculty regardless of the grant suppport. The IACUC specifically empowered by the Federal Regulations and UM Policy to manage the tensions and conflicts.

41. The IACUC and Conflict Management • IACUC has the oversight responsibility for all animal use at the Organization. • Manages interests of the “Public” vs other competing interests. • Makes sure the investigators consider the interests of the animals. • Reviews animal activities for sound experimental design and the 3Rs. • Insures the veterinary program is not unduly influenced by the organization. • Insures that institutions commit appropriate funding to support the mission of the Animal Use Program. • Independently investigates non-compliance. • Can suspend activities that are not being conducted ethically and put animals at risk.

42. The IACUC and Conflict Management • IACUC Reports the good, the bad and ugly to: • Institutional Official • OLAW and USDA • Follow - up • IACUC appointed by highest institutional authority. • Protect the University’s interests • Manage the CoI • Maintain the Public’s trust

43. Research Ethics EducationCITI Program • Human Subjects Protection • Good Clinical Practice. • Lab Animal Welfare. • Responsible Conduct of Research. • Bio-safety and Bio-security • Human Subjects Protection • Good Clinical Practice. • Lab Animal Welfare. • Responsible Conduct of Research. • Bio-safety and Bio-security • citisupport@med.miami.edu • 305 243-7970

44. CITI Laboratory Animal Welfare Program Investigators IACUC Members

45. Lab Animal Welfare Course Site Usage

46. LAW Courses 2009

47. LAW Courses Completed2009

48. www.citiprogram.org

49. Joseph Wright (September 3, 1734 - August 29, 1797), “An Experiment on a Bird in The Air Pump “ by Joseph Wright (1734-1797) British National Gallery- London